The lung is a major portal of entry for a variety of environmental, chemical, and microbiological agents. The detoxification and elimination of foreign material entering the lung is a primary role of the pulmonary macrophage. The fate of chemical carcinogens (including the polycyclic aromatic hydrocarbons) is not known. The enzyme system (aryl hydrocarbon hydroxylase, or AHH) which metabolizes these hydrocarbons is induced to high levels in pulmonary macrophages of cigarette smokers, and can be induced in vitro in cultured, mitogen-stimulated lymphocytes when culture medium contains an aromatic hydrocarbon. Prior studies indicate that patients with primary lung cancer regularly have abnormalities of AHH induction in either pulmonary macrophages or blood lymphocytes. We propose to continue to study the induction of AHH in these cells and in tissue from surgically-resected lung from lung cancer patients, and from patients with other medical problems requiring diagnostic bronchoscopy or pulmonary surgery. Responsiveness of lymphocytes from lung cancer and noncancer patients to mitogens will also be studied, to determine if any abnormalities of AHH induction can be attributed to problems of lymphocyte proliferation. Both pulmonary macrophages and cultured lymphocytes from lung cancer and noncancer patients will be studied by high pressure liquid chromotography to determine profiles of metabolites of benzo(alpha)pyrene generated during detoxification. Further efforts will be made to develop simplified and improved assay techniques for AHH, or for metabolites or aromatic hydrocarbons. By studying the ability of these cells to process carcinogenic hydrocarbons, constitutional differences may be delineated which relate to the pathogenesis of lung cancer in some patients. In addition, the detection of a dissociation between pulmonary macrophage and lymphocyte AHH induction may aid in documenting cancer in those cases where bronchoscopy fails to establish the diagnosis.